Einzeltreffer — DigiBib

Introduction: The pathogenesis of Post-Transplant Diabetes Mellitus (PTDM) is complex and multifactorial and it resembles that of Type-2 Diabetes Mellitus (T2DM). One risk factor specific to PTDM differentiates both entities: the use of immunosuppressive therapy. Specifically, Tacrolimus interacts with obesity and insulin resistance (IR) in accelerating the onset of PTDM. In a genotypic model of IR, the obese Zucker rats, Tacrolimus is highly diabetogenic by promoting the same changes in beta-cell already modified by IR. Nevertheless, genotypic animal models have their limitations and may not resemble the real pathophysiology of diabetes. In this study, we have evaluated the interaction between beta-cell damage and Tacrolimus in a non-genotypic animal model of obesity and metabolic syndrome.

Methods: Sprague Dawley rats were fed a high-fat enriched diet during 45 days to induce obesity and metabolic dysregulation. On top of this established obesity, the administration of Tacrolimus (1mg/kg/day) during 15 days induced severe hyperglycaemia and changes in morphological and structural characteristics of the pancreas.

Results: Obese animals administered with Tacrolimus showed increased size of islets of Langerhans and reduced beta-cell proliferation without changes in apoptosis. There were also changes in beta-cell nuclear factors such as a decrease in nuclear expression of MafA and a nuclear overexpression of FoxO1A, PDX-1 and NeuroD1. These animals also showed increased levels of pancreatic insulin and glucagon.

Discussion: This model could be evidence of the relationship between the T2DM and PTDM physiopathology and, eventually, the model may be instrumental to study the pathogenesis of T2DM.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Titel:	Induction of diabetes by Tacrolimus in a phenotypic model of obesity and metabolic syndrome.
Autor/in / Beteiligte Person:	Teixidó-Trujillo, S ; Porrini, E ; Menéndez-Quintanal, LM ; Torres-Ramírez, A ; Fumero, C ; Rodríguez-Rodríguez, AE
Link:	Full Text Finder (Volltext)
Zeitschrift:	Frontiers in endocrinology, Jg. 15 (2024-04-29), S. 1388361
Veröffentlichung:	[Lausanne : Frontiers Research Foundation], 2024
Medientyp:	academicJournal
ISSN:	1664-2392 (print)
DOI:	10.3389/fendo.2024.1388361
Schlagwort:	Animals Rats Male Immunosuppressive Agents adverse effects Immunosuppressive Agents pharmacology Insulin-Secreting Cells metabolism Insulin-Secreting Cells pathology Insulin-Secreting Cells drug effects Phenotype Diabetes Mellitus, Type 2 metabolism Diabetes Mellitus, Type 2 pathology Diabetes Mellitus, Experimental pathology Diabetes Mellitus, Experimental metabolism Insulin Resistance Diet, High-Fat adverse effects Tacrolimus pharmacology Metabolic Syndrome metabolism Metabolic Syndrome pathology Metabolic Syndrome chemically induced Obesity metabolism Obesity pathology Rats, Sprague-Dawley Disease Models, Animal
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Front Endocrinol (Lausanne)] 2024 Apr 29; Vol. 15, pp. 1388361. <i>Date of Electronic Publication: </i>2024 Apr 29 (<i>Print Publication: </i>2024). MeSH Terms: Tacrolimus* / pharmacology ; Metabolic Syndrome* / metabolism ; Metabolic Syndrome* / pathology ; Metabolic Syndrome* / chemically induced ; Obesity* / metabolism ; Obesity* / pathology ; Rats, Sprague-Dawley* ; Disease Models, Animal* ; Animals ; Rats ; Male ; Immunosuppressive Agents / adverse effects ; Immunosuppressive Agents / pharmacology ; Insulin-Secreting Cells / metabolism ; Insulin-Secreting Cells / pathology ; Insulin-Secreting Cells / drug effects ; Phenotype ; Diabetes Mellitus, Type 2 / metabolism ; Diabetes Mellitus, Type 2 / pathology ; Diabetes Mellitus, Experimental / pathology ; Diabetes Mellitus, Experimental / metabolism ; Insulin Resistance ; Diet, High-Fat / adverse effects References: Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13217-22. (PMID: 25157166) ; ISRN Obes. 2013 May 20;2013:584547. (PMID: 24555150) ; Clin Med (Lond). 2019 Sep;19(5):392-395. (PMID: 31530687) ; Front Endocrinol (Lausanne). 2013 Mar 27;4:37. (PMID: 23542897) ; Lab Anim Res. 2021 Aug 24;37(1):23. (PMID: 34429169) ; J Clin Invest. 2013 Aug;123(8):3305-16. (PMID: 23863625) ; Indian J Med Res. 2007 Mar;125(3):451-72. (PMID: 17496368) ; Nutr Neurosci. 2019 Jan;22(1):19-28. (PMID: 28721750) ; Am J Physiol Gastrointest Liver Physiol. 2021 Jun 1;320(6):G1014-G1033. (PMID: 33881354) ; Stem Cell Res Ther. 2020 Oct 29;11(1):459. (PMID: 33121533) ; Int J Mol Sci. 2021 Jun 23;22(13):. (PMID: 34201511) ; J Diabetes Res. 2021 Feb 23;2021:5123241. (PMID: 33708999) ; Nat Genet. 1999 Nov;23(3):323-8. (PMID: 10545951) ; Stem Cell Res Ther. 2017 Nov 2;8(1):240. (PMID: 29096722) ; Exp Physiol. 2022 Apr;107(4):265-282. (PMID: 35178802) ; Am J Transplant. 2013 Jul;13(7):1665-75. (PMID: 23651473) ; Diabet Med. 2005 Apr;22(4):359-70. (PMID: 15787657) ; Am J Transplant. 2017 Nov;17(11):2829-2840. (PMID: 28432716) ; Int J Mol Sci. 2021 Sep 01;22(17):. (PMID: 34502413) ; Endocr J. 2007 Aug;54(4):507-15. (PMID: 17510498) ; Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19090-5. (PMID: 19855005) ; J Clin Endocrinol Metab. 2003 May;88(5):2300-8. (PMID: 12727989) ; Biochem Biophys Res Commun. 2017 Jan 29;483(1):418-424. (PMID: 28017717) ; Endocrinology. 2020 Nov 1;161(11):. (PMID: 32894758) ; Cell Metab. 2010 Apr 7;11(4):298-310. (PMID: 20374962) ; Front Genet. 2015 Aug 07;6:251. (PMID: 26300908) ; J Chromatogr Sci. 2014 Jan;52(1):59-67. (PMID: 23264321) ; Dev Dyn. 2005 Jul;233(3):946-53. (PMID: 15906379) ; Diabetes. 1982 Aug;31(8 Pt 1):694-700. (PMID: 6131002) ; Nat Rev Endocrinol. 2013 Oct;9(10):615-23. (PMID: 23959366) ; Life Metab. 2023 Jun;2(3):. (PMID: 37485302) ; Front Mol Biosci. 2022 Dec 15;9:1091757. (PMID: 36589234) ; Curr Diabetes Rev. 2014 Mar;10(2):131-45. (PMID: 24809394) ; Nephrol Dial Transplant. 2016 Mar;31(3):495-505. (PMID: 26538615) ; Islets. 2022 Dec 31;14(1):114-127. (PMID: 35348048) ; Sci Rep. 2019 Dec 20;9(1):19556. (PMID: 31862918) ; Int J Mol Sci. 2021 Sep 24;22(19):. (PMID: 34638652) ; Exp Ther Med. 2021 Jul;22(1):707. (PMID: 34007316) ; Korean J Transplant. 2020 Dec 31;34(4):213-237. (PMID: 35770107) ; Br J Pharmacol. 2012 Jun;166(3):877-94. (PMID: 22352879) ; Curr Protoc Toxicol. 2020 Jun;84(1):e92. (PMID: 32436620) ; Biomolecules. 2022 Mar 31;12(4):. (PMID: 35454124) ; Diabetologia. 2011 Jul;54(7):1720-5. (PMID: 21465328) ; Curr Med Chem. 2009;16(24):3144-51. (PMID: 19689288) Contributed Indexing: Keywords: Tacrolimus; animal model; metabolic syndrome; obesity; post-transplant diabetes; type 2 diabetes Entry Date(s): Date Created: 20240515 Date Completed: 20240515 Latest Revision: 20240516 Update Code: 20240516 PubMed Central ID: PMC11092379

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Induction of diabetes by Tacrolimus in a phenotypic model of obesity and metabolic syndrome.